Variant 10-7171963-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001387889.1(SFMBT2):c.2347G>A(p.Gly783Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,494,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

SFMBT2
NM_001387889.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0180

Variant links:

Genes affected

SFMBT2 (HGNC:20256): (Scm like with four mbt domains 2) Enables histone binding activity. Involved in negative regulation of gene expression. Located in aggresome; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SFMBT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028353363).

BP6

Variant 10-7171963-C-T is Benign according to our data. Variant chr10-7171963-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2359714.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFMBT2	NM_001387889.1 linkuse as main transcript	c.2347G>A	p.Gly783Arg	missense_variant	19/21	ENST00000397167.6	NP_001374818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFMBT2	ENST00000397167.6 linkuse as main transcript	c.2347G>A	p.Gly783Arg	missense_variant	19/21	5	NM_001387889.1	ENSP00000380353	P4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000521

AC:

AN:

1342764

Hom.:

Cov.:

AF XY:

0.00000456

AC XY:

AN XY:

658522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000682

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000473

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000145

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.000506

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000989

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.78

DANN

Benign

0.61

DEOGEN2

Benign

0.0081

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.13

.;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.1

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.030

Sift

Benign

0.82

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0

B;B

Vest4

0.063

MutPred

0.36

Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);

MVP

0.043

MPC

1.2

ClinPred

0.052

GERP RS

-11

Varity_R

0.025

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over